Transplantation and Stem Cell Therapy for Cerebellar Degenerations

Abstract

Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration.

Evaluation of the spatial arrangement of Purkinje cells in ataxic rat’s cerebellum after Sertoli cells transplantation

“…Cell therapy is a promising treatment to replace degenerated cells and has some trophic effects [4]. Transplantation of some stem cells has been tested in the treatment of ataxia [5,16].…”

Smaller Absolute Quantities but Greater Relative Densities of Microvessels Are Associated with Cerebellar Degeneration in Lurcher Mice

“…Its functional effect was explained by the reconstruction of the neural circuitries (Sotelo and Alvarado-Mallart, 1987 ). However, neurotransplantation still needs in-depth investigation before it can become a routine method in humans (Cendelin et al, 2009 ; Babuska et al, 2015 ; Cendelin, 2016 ).…”

“…Furthermore, the abnormal density of microvessels might positively or negatively influence the regenerative potential of the tissue and may also potentially influence the treatment efficiency. Vascularization of the tissue is one of the most important factors determining features of the niche that might be of importance, for instance, for the development and functional integration of neural and stem cell grafts (Cendelin, 2016 ). In this regard, almost nothing is known about the vascular changes in cerebellar degeneration.…”

“…Cerebellar degeneration results in ataxia (Fortier et al, 1987 ) as well as various cognitive and behavioral abnormalities (Lalonde et al, 1988 ; Hilber et al, 2004 ; Cendelin et al, 2014 ; Lorivel et al, 2014 ; Tuma et al, 2015 ) in heterozygous Lurcher mice. Trophic support of damaged tissue through the host vascular bed is the simplest way for the correction and minimizing of the effects of the degeneration (Cendelin, 2016 ).…”

Cerebellum: from Fundamentals to Translational Approaches. The Seventh International Symposium of the Society for Research on the Cerebellum

“…As highlighted by Jan Cendelin, great hope exists that neurotransplantations will soon represent a viable therapeutical strategy. Studies in mutant mice are very encouraging and further experiments are needed to jump successfully to human trials in the near future [11]. Bing-wen Soong discussed in his talk the dominant ataxias with a focus on TGM6 as a novel causative gene of SCA35 and its clinical features.…”